Cyclosporins are a class of poly-N-methylated cyclic undecapeptides. The first cyclosporin to be isolated was cyclosporin A (CAS Registry Number: 59865-13-3), a naturally occurring fungal metabolite having the following structure:

As shown by the structure above, Cyclosporin A consists of 11 amino acids and can be further represented as follows:

where:
MeBmt is (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine;
αAbu is L-α-aminobutyric acid;
Sar is sarcosine;
MeLeu is N-methyl-L-leucine;
Val is L-valine;
Ala is L-alanine;
DAla is D-alanine; and
MeVal is N-methyl-L-valine.
The numbers 1-11 are used to designate each of the eleven amino acids. Thus, MeBMT is the amino acid at position 1; sarcosine, the amino acid at position 3. In certain instances, the description herein may refer to the amino acid side chain at any one of positions 1-11. The carbon to which the amino acid side chain is attached is referred to as the alpha (α) carbon.
Cyclosporin A is best known for its immunosuppressive properties and is commonly prescribed for use in patients that have undergone bone marrow or organ transplantation. The present invention relates to the discovery of water-soluble analogs of cyclosporin A that are potent inhibitors of cyclophilin.